title: Clinical significance of circulating tumor cells detected by an invasion assay in peripheral blood of patients with ovarian cancer.
abstract: OBJECTIVE
  The invasive growth of circulating tumor cells (CTCs) propagates cancer metastasis. The aims of this study were to evaluate the association of invasive CTCs, detected by a novel cell invasion assay, with disease stage, CA-125 level and patient survival.
  
  
  METHODS
  Peripheral blood samples from 71 patients undergoing evaluation for ovarian malignancy were assessed for the presence of invasive CTCs using a cell invasion assay that enriches and identifies tumor cells with a cell adhesion matrix (CAM). Invasive CTCs were identified as cells exhibiting CAM invasion (CAM+) and expressing standard epithelial markers (Epi+).
  
  
  RESULTS
  43 (60.6%) patients had detectable CTCs: 0/5 benign patients, 1/10 (10%) early stage, 39/52 (73.1%) late stage and 3/4 (75%) unstaged patients (p-value <0.001). CTC counts ranged from 0-149 CTCs/ml with stage III/IV patients exhibiting significantly higher mean counts (41.3 CTCs/ml) than stage I/II patients (6.0 CTCs/ml) and benign patients (0 CTCs/ml, p-value=0.001). A positive correlation between CTC count and CA-125 level was observed (Spearman correlation coefficient r=0.309, p-value=0.035). Kaplan-Meier curves revealed a significant decrease in disease-free survival in patients with detectable CTCs (median survival 15.0 months vs. 35.0 months, log-rank p-value=0.042). Tumor grade and tumor histology did not influence CTC detection.
  
  
  CONCLUSIONS
  Invasive CTCs can be detected in a majority of epithelial ovarian cancer patients and may predict shorter disease-free survival. Furthermore, higher CTC counts may reflect later stage disease and higher CA-125 levels.
authors.affiliation: Department of Medicine, Metastasis Research Laboratory, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Fan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.forename: John J
authors.initials: JJ
authors.lastname: Chen
authors.forename: Wen-Tien
authors.initials: WT
authors.lastname: Chen
authors.forename: Michael L
authors.initials: ML
authors.lastname: Pearl
mesh_terms: D018394:CA-125 Antigen / Q000097:blood; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000097:blood / Q000473:pathology; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D018394:CA-125 Antigen